Selective Neoadjuvant Treatment According to Immunohistochemical Subtype for HER2 Negative Breast Cancer Patients

NCT00432172 | Completed Phase 2 Results

• 1 other identifier: GEICAM/2006-03
• Study Type: interventional
• Target: 189
• Locations: 1 country
• Sites: 12

Brief Summary

This is an open-label study that includes two substudies of random distribution. First,a sample of the primary tumor will be obtained and will be analyzed by an immunohistochemical technique to determine several markers.Depending on the expression of these markers, the patients will be characterize as group 1 (Luminal A phenotype) or group 2 (Basal phenotype) and a random assignment will be performed to standard or experimental treatment.

Conditions

Breast Cancer

Keywords

Her2neu negative breast cancer.; Neoadjuvant treatment.

Outcome Measures

Primary Outcomes (1)

• Pathological Response for Basal Group 2

  This primary outcome only applies for the basal group 2 as per protocol. The pathological response in luminal group 1 was not pre-specified even as a Secondary Outcome. Pathological response was assessed after surgery, according to the Miller \& Payne criteria, which stratifies the responses based on the proportion of remaining tumor and post-chemotherapy changes, evaluating separately the response in breast and axilla. Grades 1-4 are categorised as a partial pathological response (pPR) and grade 5 was a complete pathological response (cPR).

  Up to 24 weeks

Secondary Outcomes (3)

• Clinical Response Rate

  Up to week 24

• Breast Conservative Surgery Rate

  Up to 24 weeks

• Axillary Node Status at the Time of Surgery

  Up to 24 weeks

Study Arms (4)

Group 1 (Luminal A) Standard treatment

ACTIVE COMPARATOR

Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel

Group 1 (Luminal A) Selective treatment

EXPERIMENTAL

Selective treatment: Postmenopausal patients: exemestane x 6 months Premenopausal patients: goserelin x 6 months + exemestane x 6 months

Drug: Exemestane; Drug: Goserelin

Group 2 (Basal) Standard treatment

ACTIVE COMPARATOR

Standard treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv every 21 days for 4 cycles.

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel

Group 2 (Basal) Selective treatment

EXPERIMENTAL

Selective treatment: Epirubicin (E) 90 mg/ m2 intravenous (iv) in combination with Cyclophosphamide (C) 600 mg/ m2 iv every 21 days for 4 cycles, followed by docetaxel (D)100 mg/m2 iv and carboplatin (Cb) (area under the curve = 6 mg/mL) iv every 21 days for 4 cycles.

Drug: Epirubicin; Drug: Cyclophosphamide; Drug: Docetaxel; Drug: Carboplatin

Interventions

Epirubicin DRUG

Also known as: Ellence

Group 1 (Luminal A) Standard treatment; Group 2 (Basal) Selective treatment; Group 2 (Basal) Standard treatment

Cyclophosphamide DRUG

Also known as: Cytoxan

Group 1 (Luminal A) Standard treatment; Group 2 (Basal) Selective treatment; Group 2 (Basal) Standard treatment

Docetaxel DRUG

Also known as: Taxotere

Group 1 (Luminal A) Standard treatment; Group 2 (Basal) Selective treatment; Group 2 (Basal) Standard treatment

Exemestane DRUG

Also known as: aromasil

Group 1 (Luminal A) Selective treatment

Goserelin DRUG

Also known as: Zoladex

Group 1 (Luminal A) Selective treatment

Carboplatin DRUG

Also known as: Paraplatin

Group 2 (Basal) Selective treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent.
• Breast cancer with histological diagnosis.
• Negative Human Epidermal Growth Factor Receptor 2 (HER2) tumours defined as immunohistochemistry (IHQ) 0,1+.
• No evidence of suspicion of metastatic disease.
• Age \>= 18 years old.
• Performance status (Karnofsky index) \>= 80 (ECOG 0,1).
• Adequate cardiac function by ECG in the previous 12 weeks.
• Hematology: neutrophils \>= 1,5 x10\^9/l; platelets \>= 100 x10\^9/l; hemoglobin \>= 10 g/dl.
• Adequate hepatic function: total bilirubin \<= 1x Upper Normal Limit (UNL); Aspartate aminotransferase (AST) (SGOT) and Alanine aminotransferase (ALT) (SGPT) \<= 2.5 x UNL; alkaline phosphatase \<= 2.5 x UNL.
• Adequate renal function: creatinine \<= 1 x UNL; creatinine clearance \>= 60 ml/min.
• Patients able to comply with study treatment and follow-up.
• Negative pregnancy test in the previous 14 days.

You may not qualify if:

• HER2 positive tumours (defined as IHQ 3+ or positive fluorescence in situ hybridization \[FISH\]).
• Prior systemic therapy for breast cancer (immunotherapy, hormonotherapy, chemotherapy).
• Prior treatment with anthracyclines or taxanes (paclitaxel, docetaxel) for any previous malignancy.
• Prior radiotherapy for breast cancer.
• Bilateral invasive breast cancer.
• Pregnant or lactating women.
• Previous grade \>= 2 motor or sensorial neurotoxicity (National Cancer Institute Common Toxicity Criteria \[NCICTC\]).
• Other serious comorbidities: congestive heart failure or unstable angina; prior history of myocardial infarction in previous year; uncontrolled hypertension (HT); high risk arrhythmias; history of significant neurological or psychiatric disorders; uncontrolled active infection; active peptic ulcer; unstable diabetes mellitus; dyspnea at rest; or chronic therapy with oxygen.
• Previous or current history of neoplasms different from breast cancer, except for skin carcinoma, cervical in situ carcinoma, or any other tumor curatively treated and without recurrence in the last 10 years; ductal in situ carcinoma in the same breast; lobular in situ carcinoma.
• Chronic treatment with corticosteroids.
• Contraindications for administration of corticosteroids.
• Concomitant treatment with other therapy for cancer.
• Males.

Sponsors & Collaborators

• Spanish Breast Cancer Research Group: lead
• Pfizer: collaborator

Study Sites (12)

Corporació Sanitaria Parc Taulí

Sabadell, Barcelona, 08208, Spain

Location

Hospital Mutua de Terrassa

Terrassa, Barcelona, 08221, Spain

Location

Onkologikoa

Donostia / San Sebastian, Gipuzkoa, 20014, Spain

Location

Complejo Hospitalario Universitario A Coruña

A Coruña, 15006, Spain

Location

Centro Oncológico Regional de Galicia

A Coruña, 15009, Spain

Location

Hospital General de Alicante

Alicante, 03010, Spain

Location

Hospital del Mar

Barcelona, 08003, Spain

Location

Hospital Universitario Reina Sofía

Córdoba, 14004, Spain

Location

Complejo Hospitalario de Jaén

Jaén, 23007, Spain

Location

Hospital de la Princesa

Madrid, 28006, Spain

Location

Hospital Clínico Universitario Virgen de la Victoria

Málaga, 29010, Spain

Location

Hospital Clínico Universitario de Valencia

Valencia, 46010, Spain

Location

Related Publications (8)

• Alba E, Chacon JI, Lluch A, Anton A, Estevez L, Cirauqui B, Carrasco E, Calvo L, Segui MA, Ribelles N, Alvarez R, Sanchez-Munoz A, Sanchez R, Garcia-Asenjo JA, Rodriguez-Martin C, Escudero MJ, Albanell J. A randomized phase II trial of platinum salts in basal-like breast cancer patients in the neoadjuvant setting. Results from the GEICAM/2006-03, multicenter study. Breast Cancer Res Treat. 2012 Nov;136(2):487-93. doi: 10.1007/s10549-012-2100-y. Epub 2012 Oct 9.

  PMID: 23053638 RESULT

• Alba E, Calvo L, Albanell J, De la Haba JR, Arcusa Lanza A, Chacon JI, Sanchez-Rovira P, Plazaola A, Lopez Garcia-Asenjo JA, Bermejo B, Carrasco E, Lluch A; GEICAM. Chemotherapy (CT) and hormonotherapy (HT) as neoadjuvant treatment in luminal breast cancer patients: results from the GEICAM/2006-03, a multicenter, randomized, phase-II study. Ann Oncol. 2012 Dec;23(12):3069-3074. doi: 10.1093/annonc/mds132. Epub 2012 Jun 6.

  PMID: 22674146 RESULT

• Prat A, Lluch A, Albanell J, Barry WT, Fan C, Chacon JI, Parker JS, Calvo L, Plazaola A, Arcusa A, Segui-Palmer MA, Burgues O, Ribelles N, Rodriguez-Lescure A, Guerrero A, Ruiz-Borrego M, Munarriz B, Lopez JA, Adamo B, Cheang MC, Li Y, Hu Z, Gulley ML, Vidal MJ, Pitcher BN, Liu MC, Citron ML, Ellis MJ, Mardis E, Vickery T, Hudis CA, Winer EP, Carey LA, Caballero R, Carrasco E, Martin M, Perou CM, Alba E. Predicting response and survival in chemotherapy-treated triple-negative breast cancer. Br J Cancer. 2014 Oct 14;111(8):1532-41. doi: 10.1038/bjc.2014.444. Epub 2014 Aug 7.

  PMID: 25101563 RESULT

• Prat A, Lluch A, Turnbull AK, Dunbier AK, Calvo L, Albanell J, de la Haba-Rodriguez J, Arcusa A, Chacon JI, Sanchez-Rovira P, Plazaola A, Munoz M, Pare L, Parker JS, Ribelles N, Jimenez B, Bin Aiderus AA, Caballero R, Adamo B, Dowsett M, Carrasco E, Martin M, Dixon JM, Perou CM, Alba E. A PAM50-Based Chemoendocrine Score for Hormone Receptor-Positive Breast Cancer with an Intermediate Risk of Relapse. Clin Cancer Res. 2017 Jun 15;23(12):3035-3044. doi: 10.1158/1078-0432.CCR-16-2092. Epub 2016 Nov 30.

  PMID: 27903675 RESULT

• Alba E, Lluch A, Ribelles N, Anton-Torres A, Sanchez-Rovira P, Albanell J, Calvo L, Garcia-Asenjo JA, Palacios J, Chacon JI, Ruiz A, De la Haba-Rodriguez J, Segui-Palmer MA, Cirauqui B, Margeli M, Plazaola A, Barnadas A, Casas M, Caballero R, Carrasco E, Rojo F. High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer. Oncologist. 2016 Feb;21(2):150-5. doi: 10.1634/theoncologist.2015-0312. Epub 2016 Jan 19.

  PMID: 26786263 RESULT

• Chin SF, Santonja A, Grzelak M, Ahn S, Sammut SJ, Clifford H, Rueda OM, Pugh M, Goldgraben MA, Bardwell HA, Cho EY, Provenzano E, Rojo F, Alba E, Caldas C. Shallow whole genome sequencing for robust copy number profiling of formalin-fixed paraffin-embedded breast cancers. Exp Mol Pathol. 2018 Jun;104(3):161-169. doi: 10.1016/j.yexmp.2018.03.006. Epub 2018 Mar 31.

  PMID: 29608913 RESULT

• Santonja A, Sanchez-Munoz A, Lluch A, Chica-Parrado MR, Albanell J, Chacon JI, Antolin S, Jerez JM, de la Haba J, de Luque V, Fernandez-De Sousa CE, Vicioso L, Plata Y, Ramirez-Tortosa CL, Alvarez M, Llacer C, Zarcos-Pedrinaci I, Carrasco E, Caballero R, Martin M, Alba E. Triple negative breast cancer subtypes and pathologic complete response rate to neoadjuvant chemotherapy. Oncotarget. 2018 May 29;9(41):26406-26416. doi: 10.18632/oncotarget.25413. eCollection 2018 May 29.

  PMID: 29899867 RESULT

• Ocana A, Chacon JI, Calvo L, Anton A, Mansutti M, Albanell J, Martinez MT, Lahuerta A, Bisagni G, Bermejo B, Semiglazov V, Thill M, Chan A, Morales S, Herranz J, Tusquets I, Chiesa M, Caballero R, Valagussa P, Bianchini G, Alba E, Gianni L. Derived Neutrophil-to-Lymphocyte Ratio Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Breast Cancer. Front Oncol. 2022 Feb 11;11:827625. doi: 10.3389/fonc.2021.827625. eCollection 2021.

  PMID: 35223459 RESULT

Related Links

• Spanish Breast Cancer Research Group (GEICAM) is a Spanish Breast Cancer Research Group

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Epirubicin; Cyclophosphamide; Docetaxel; exemestane; Goserelin; Carboplatin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Doxorubicin; Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates; Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Phosphoramides; Organophosphorus Compounds; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Diterpenes; Terpenes; Gonadotropin-Releasing Hormone; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Coordination Complexes

Results Point of Contact

• Title: Scientific Director / Medical Lead / Project Manager
• Organization: Spanish Breast Cancer Research Group

geicam@geicam.org

+34916592870

Study Officials

• Study Director

  Hospital Miguel Servet

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2007
• First Posted: February 7, 2007
• Study Start: April 24, 2007
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: April 3, 2023
• Results First Posted: July 17, 2019

Record last verified: 2023-03

Locations

ES (12)